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Soy isoflavones decrease the catechol-O-methyltransferase-mediated inactivation of 4-hydroxyestradiol in cultured

Leane Lehmann1, Ling Jiang, Jörg Wagner

  • 1Institute of Applied Biosciences, Section of Food Chemistry, University of Karlsruhe, Kaiserstrasse 12, D-76131 Karlsruhe, Germany. leane.lehmann@lmc.uni-karlsruhe.de

Carcinogenesis
|January 15, 2008
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Soy isoflavones, found in supplements, significantly reduce catechol-O-methyltransferase (COMT) gene expression and activity in breast cancer cells. This finding suggests a potential link between diet and hormonal carcinogenesis, impacting estrogen metabolism.

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Area of Science:

  • Endocrinology
  • Molecular Biology
  • Nutritional Science

Background:

  • Hormonal carcinogenesis involves 17beta-estradiol (E2) and its metabolites, influenced by enzymes like catechol-O-methyltransferase (COMT).
  • COMT is crucial for inactivating catechol estrogens in the mammary gland.
  • The cancer-protective role of soy isoflavones is debated, necessitating investigation into their molecular mechanisms.

Purpose of the Study:

  • To investigate the effect of soy isoflavones (genistein, daidzein) on COMT gene expression and activity.
  • To explore the role of the estrogen receptor (ER) in mediating these effects.
  • To understand how soy isoflavones might influence the detoxification of estrogen metabolites in breast cancer cells.

Main Methods:

  • Cultured human mammary adenocarcinoma MCF-7 cells were treated with soy isoflavones.
  • COMT messenger RNA (mRNA) levels were quantified using reverse transcription/competitive polymerase chain reaction.
  • COMT activity was measured via high-performance liquid chromatography (HPLC) using quercetin and 4-hydroxyestradiol (4-HO-E2) as substrates.
  • Estrogen receptor involvement was assessed using the antagonist ICI 182,780.

Main Results:

  • Soy isoflavones significantly reduced COMT mRNA levels and COMT activity in MCF-7 cells.
  • The methylation of 4-hydroxyestradiol (4-HO-E2) was also inhibited by soy isoflavones.
  • The estrogen receptor antagonist ICI 182,780 indicated that the estrogen receptor mediates the down-regulation of COMT expression by soy isoflavones.

Conclusions:

  • Hormonally active concentrations of soy isoflavones inhibit the detoxification of catechols by reducing COMT expression and activity in a human breast cancer cell line.
  • Dietary soy isoflavones may play a significant role in modulating COMT activity, potentially influencing hormonal carcinogenesis.
  • Further research is warranted to elucidate the full implications of these findings for breast cancer prevention and treatment.